title: Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony-stimulating factor support for patients with poor-prognosis cancer of the head and neck.
abstract: OBJECTIVE
  We have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX). In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients.
  
  
  METHODS
  Fifty-five patients who had either failed to respond to prior RT (n = 25) or surgery, had a coexistent or prior second malignancy, or who had unresectable or metastatic disease and an expected 2-year survival rate less than 10%, were treated. Chemoradiotherapy consisted of 2 Gy on days 2 to 6 (once-daily RT cohorts) or 1.5 Gy twice a day (hyperfractionated cohorts). Simultaneous HU (500 or 1,000 mg twice per day for 11 doses) and infusional 5-FU (600-800 mg/m2/d for 5 days) were given along with infusional paclitaxel at escalating doses of 5 to 25 mg/m2/d for 5 days. Granulocyte colony-stimulating factor (G-CSF) was administered on days 7 through 13 at 5 microg/kg/d. Cycles were repeated every 14 days until completion of RT. Plasma paclitaxel levels were determined on day 4 of cycle 1.
  
  
  RESULTS
  Dose-limiting toxicities (DLTs) consisted of myelosuppression, mucositis, dermatitis, and diarrhea. Plasma concentrations of paclitaxel greater than 10 nmol/L were achieved in 65% of patients at the recommended phase II dose (RPTD) level of paclitaxel. Seventy percent of assessable patients achieved a complete response (CR) to therapy. Twenty patients were treated at the RPTD of HU 500 mg orally twice daily for 11 doses, 5-FU 600 mg/m2/d by continuous infusion for 5 days; and paclitaxel 20 mg/m2/d by continuous infusion for 5 days, with twice-daily RT.
  
  
  CONCLUSIONS
  The addition of infusional paclitaxel and hyperfractionated RT to FHX is feasible. Radiosensitizing levels of paclitaxel are achieved in most patients. The high locoregional control rate of this regimen justifies further investigation in previously untreated patients.
authors.affiliation: Section of Hematology/Oncology, University of Chicago Department of Medicine, IL, USA. bebrocks@reis.bsd.uchicago
authors.forename: B
authors.initials: B
authors.lastname: Brockstein
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: K
authors.initials: K
authors.lastname: Stenson
authors.forename: A
authors.initials: A
authors.lastname: Fasanmade
authors.forename: R
authors.initials: R
authors.lastname: Stupp
authors.forename: B
authors.initials: B
authors.lastname: Glisson
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: L
authors.initials: L
authors.lastname: Sulzen
authors.forename: A
authors.initials: A
authors.lastname: Klepsch
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D005472:Fluorouracil; D006918:Hydroxyurea